DNA methylation profiling in Barrett's esophagus and esophageal adenocarcinoma reveals unique methylation signatures and molecular subclasses
DNA methylation profiling in Barrett's esophagus and esophageal adenocarcinoma reveals unique methylation signatures and molecular subclasses
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DOI：
10.4161/epi.6.12.18199
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发表时间：
2011-12-01
期刊：
影响因子：
3.7
通讯作者：
Grady, William M.
中科院分区：
文献类型：
--
作者：
Kaz, Andrew M.;Wong, Chao-Jen;Grady, William M.
Barrett食管（BE）是一种化生过程，其中正常的复层鳞状食管上皮被特化的肠上皮取代。Barrett's是食管腺癌（EAC）唯一被接受的前驱病变，EAC是一种在西方国家发病率迅速增加的实体瘤。BE通过中间步骤演变为EAC，这些步骤涉及发育不良程度的增加。目前的组织学标准是相当主观的，BE的临床表现是高度可变的，难以预测使用这些标准。人们普遍认为，BE和EAC中存在的分子改变将为这些疾病提供比目前使用的临床和组织学特征更精确的预后和预测标志物。为了进一步确定能够对BE和EAC的独特组进行分类的分子改变，我们利用甲基化微阵列来比较正常鳞状细胞、BE、BE+高度异型增生（HGD）和EAC病例的集合的总体基因甲基化状态。我们发现了不同的全球甲基化签名，以及特定基因的差异甲基化，区分这些组织学组。我们还注意到BE和EAC病例中的高和低甲基化表观基因型。对区分BE与BE + HGD和EAC的那些CpG位点的额外验证可能导致发现有用的生物标志物，其在BE和EAC的诊断和预后中具有潜在的临床应用。
Barrett's esophagus (BE) is a metaplastic process whereby the normal stratified, squamous esophageal epithelium is replaced by specialized intestinal epithelium. Barrett's is the only accepted precursor lesion for esophageal adenocarcinoma (EAC), a solid tumor that is rapidly increasing in incidence in western countries. BE evolves into EAC through intermediate steps that involve increasing degrees of dysplasia. Current histologic criteria are quite subjective and the clinical behavior of BE is highly variable and difficult to predict using these standards. It is widely believed that molecular alterations present in BE and EAC will provide more precise prognostic and predictive markers for these conditions than the current clinical and histologic features in use. In order to further define molecular alterations that can classify unique groups of BE and EAC, we utilized methylation microarrays to compare the global gene methylation status of a collection of normal squamous, BE, BE+ high-grade dysplasia (HGD) and EAC cases. We found distinct global methylation signatures, as well as differential methylation of specific genes, that discriminated these histological groups. We also noted high and low methylation epigenotypes among the BE and EAC cases. Additional validation of those CpG sites that distinguished BE from BE + HGD and EAC may lead to the discovery of useful biomarkers with potential clinical applications in the diagnosis and prognosis of BE and EAC.